Screening for precancerous anal lesions linked to human papillomaviruses: French recommendations for clinical practice.

In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.

[Rieger-Marchac flaps: Complications and patient satisfaction]. / Le lambeau de Rieger-Marchac : complications et satisfaction des patients.

PURPOSE: Like all surgical procedures, dorsal nasal flaps may be followed by both early and late complications. The aim of this study was to evaluate the surgical complications and cosmetic outcome of dorsal nasal flaps over a 7-year period in an academic dermatologic surgery unit. PATIENTS AND METHODS: Data were collected retrospectively for all patients undergoing dorsal nasal flap between 1 January 2006 and 31 December 2013. Early and late complications were recorded. Patients were contacted by phone to assess long-term outcomes. RESULTS: A total of 35 patients were included. Early complications included bleeding (n=2), local infection (n=2) and focal flap necrosis (n=1). Late complications comprised flap thickening (n=7), restriction of the medial canthus (n=2), opening of the labionasal angle (n=1), stitch granuloma (n=1) and telangiectasia on the flap (n=1). Regarding the aesthetic result, seven patients were very satisfied with the flap. Four patients underwent corrective surgery and one patient had laser treatment for telangiectasia on the flap. CONCLUSION: Two thirds of patients were satisfied with the aesthetic results and one third had late complications of the flap. Consequently, patients undergoing Rieger-Marchac procedures must be informed of the potential need for further corrective measures following nasal dorsal flap repair.

A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris.

BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with Kaposi's sarcoma-associated herpesvirus (KSHV). In low-endemic countries, KSHV infects predominantly men having sex with men (MSM). OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low-endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors. METHODS: Retrospective single-centre study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analyses to determine aggressiveness of CKS. RESULTS: Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years; sex ratio (M/F) was 6.4, and 28% were MSM; MSM patients were younger (P = 0.02), less often originated from endemic areas (P < 0.0001). KS was less severe (P = 0.04), required more often a local treatment than a systemic one (P = 0.03). On multivariate analysis, CD4 T-cell count > 500/mm3 at baseline was associated with a reduced risk of severe evolution. CONCLUSION: First CKS cohort in low-endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

[Dermatologic surgery, hemophilia and Von Willebrand disease]. / Risques en dermatologie interventionnelle chez les patients hémophiles ou atteints de la maladie de Willebrand.

BACKGROUND: Von Willebrand disease (VWD) and hemophilia A and B are the most common types of hereditary coagulation-factor deficiencies. The frequency and type of complications of skin surgery in these patients are unknown. The increasing incidence of skin cancer prompted us to reflect upon this issue. While the incidence of skin cancer is increasing, the complications of skin surgery or ablative laser treatment remain unknown in this population. AIM: The aim of this study was to determine the frequency of bleeding complications during and after skin surgery in patients with a hereditary coagulation-factor deficiency (hemophilia or VWD). PATIENTS AND METHODS: We conducted a retrospective study in patients with hemophilia A or B or VWD undergoing skin surgery or ablative laser treatment at the Dermatology Department of the Cochin Hospital in Paris, France. RESULTS: Fourteen procedures were performed in 8 patients. Three episodes of bleeding occurred (n=3/14, 21.4%): one hematoma, one delayed bleed and one immediate bleed. None of these complications required surgical revision or resuscitation. DISCUSSION: The rate of hemorrhagic complications was higher than in the general population. However, these complications can be considered non-serious and the risk-benefit ratio remains favorable. Multidisciplinary management and coordination with the reference hemophilia center are mandatory in this population to establish a coagulation-factor (CF) substitution protocol suited to the disease characteristics and the surgical procedure.

[CONDYDAV: A multicentre observational study of patients presenting external genital warts in France]. / CONDYDAV : étude observationnelle multicentrique des patients présentant des condylomes dans les dispensaires antivénériens en France.

BACKGROUND: Since 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear. OBJECTIVES: To determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination. PATIENTS AND METHODS: In this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France. RESULTS: A total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil® and one with Cervarix®. Cryotherapy was the preferred treatment. CONCLUSION: With the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.

Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy.

BACKGROUND: Sentinel lymph-node (LN) biopsy (SLNB) is a valuable tool to assess the regional LN status in Merkel cell carcinoma (MCC). However, its prognostic value is still debated. This study was undertaken to assess SLNB usefulness for MCC management and to determine the impact of SLNB status on disease-free survival (DFS) and overall survival (OS) by comparing SLNB-positive versus -negative patients according to demographic, clinical and treatment characteristics. PATIENTS AND METHODS: In this retrospective, multicenter observational study, SLNB was proposed to all patients referred for clinically N0 MCC. Treatment schedule consisted of wide-margin surgical resection of primary MCC followed by adjuvant radiation therapy (aRT) to the primary site and, for SLNB-positive patients, radical LN dissection followed by regional aRT. Univariate and multivariate analyses determined factors associated with DFS and OS. RESULTS: Among 87 patients with successful SLNB, 21 (24.1%) were SLNB-positive. Median follow-up for the entire series was 39 months; respective 3-year DFS and OS rates were 73% and 81.4%, respectively. Univariate analysis (all patients) identified SLNB-negativity as being associated with prolonged OS (P = 0.013) and aRT (all sites considered) was associated with longer DFS (P = 0.004) and OS (P = 0.018). Multivariate analysis (all patients) retained SLNB status and aRT (all sites considered) as being associated with improved DFS (P = 0.014 and 0.0008) and OS (P = 0.0020 and 0.0019). Moreover, for SLNB-negative patients, tumor-bed irradiation was also significantly associated with prolonged DFS (P = 0.006) and OS (P = 0.014). CONCLUSIONS: The present study demonstrates that SLNB-negativity is a strong predictor of longer DFS and OS in stage I and II MCC patients. The similar benefit for aRT on tumor bed observed in this study has to be confirmed by a prospective study. The results advocate for SLNB being considered to all MCC patients.

[Validation study of the French schizotypal personality questionnaire in a sample of adolescents: a confirmatory factor analysis]. / Validation de la version française du questionnaire de personnalité schizotypique de Raine dans la population adolescente : étude de la structure factorielle.

AIMS: This article aims to validate the schizotypal personality questionnaire in a sample of French speaking adolescents. Because early schizotypal manifestations are predictive of psychosis-proneness, reliable self-report measures are crucial for early detection of vulnerability to schizophrenia during adolescence. Unlike most existing self-reports, the questionnaire de personnalité schizotypique (SPQ) assesses individual differences in all nine feature of DSM-IV schizotypal personality (i.e. ideas of reference, excessive social anxiety, odd beliefs, unusual perceptual experience, odd behaviour, no close friends, odd speech, constricted affect and suspiciousness). Furthermore, it yields dimensional scores concerning the main schizotypal factors, which represent valuable information for the clinician's case formulation and can be used as a screening instrument in the general population. METHOD: Our sample consisted of 174 adolescents (98 girls) between 12 and 17 years old. All completed the SPQ 74-item self-report. Participants were recruited in secondary schools in Switzerland, and through the child and adolescent community outpatient psychiatric service (office médico-pédagogique) affiliated to the University of Geneva's Psychiatry Department and to the Canton of Geneva Education Department. A confirmatory factorial analysis was conducted on our sample to test nine competing models of SPQ. The 3-factor model of Raine et al. was compared to concurrent 2, 3, and 4-factor models. Simple structure models of Raine et al. and Stefanis et al. were also tested. RESULTS: The following observations were highlighted in our results: (1) goodness-of-fit indices are better for structures allowing cross loadings than for simple structures; (2) amongst the simple structures, the best goodness-of-fit index was obtained for the Raine model and (3) the fit between our data and the Raine model is improved by a cross loading for suspiciousness subscale. The latter seems problematic for the global data fitting. This led us to test simple structures models of Siever and Gunderson, Raine et al., and Stefanis et al., based on eight subscales rather than nine. Without suspiciousness subscale, goodness-of-fit indices are enhanced in these three models. The 3-factor model yields the clearest and most reliable results in comparison with other competing models. In summary, the best goodness-of-fit indices were obtained for the 3-factor Raine model. Goodness-of-fit indices could be improved by the exclusion of the suspiciousness scale. CONCLUSIONS: Consistent with earlier analyses by Raine et al. and Dumas et al., our data confirm the 3-factor model of the SPQ (cognitive-perceptive; interpersonal; disorganized) in a sample of French speaking adolescents. Our analyses confirm that two dimensions are insufficient to explain the structure of schizotypy during adolescence. These results further suggest the stability of a 3-factor structure during lifespan. We note that the inclusion of the suspiciousness subscales engenders statistical issues. Most studies to date have dealt with these issues by performing a cross-loading with this subscale, or by the inclusion of a paranoid factor which is linked with the negative and the cognitive-perceptive factors. We found that the most statistically sound strategy was reached without the inclusion of the suspiciousness subscale. Future studies with larger samples could investigate the SPQ structure at an item-level, which carries the benefit of reduced restrictions on the factorial analysis. In conclusion, the current study shows that the French version SPQ constitutes a reliable self-report questionnaire for the assessment of schizotypal trait expression during adolescence that may assist in the evaluation of psychosis proneness in youths.

[Cholesterol crystal emboli presenting as a mononeuropathy]. / Maladie des embolies de cristaux de cholestérol révélée par un tableau de mononeuropathie.

Cholesterol crystal embolism is observed in polyvascular patients usually following a medical procedure. We report a 93-year-old patient with lower limb mononeuropathy in whom cholesterol crystal embolism was confirmed by neuromuscular biopsy. Previously, an ophthalmoscopy and a livedo biopsy had been performed and the results were normal. Mononeuropathy simplex or multiplex is a clinical expression for cholesterol crystal embolism that may thus be confounded with polyarteritis nodosa. Neuromuscular biopsy can provide accurate diagnosis if other investigations are inconclusive.

Mice's brain radioprotection: comparative efficacy of a series of aminothiols and aminothiol precursors.

A serie of radioprotective aminothiols was checked upon irradiation of the mice's brain. Cysteamine protects efficiently the brain as soon as 15 minutes after its administration. Among the tested aminothiols, it was the most effective compound. 2-isopropyl 1,3-thiazolane, rapidly hydrolysed, delivers a large amount of cysteamine in the brain and was nearly as potent as exogenous cysteamine. The other thiazolanes which delivered only progressively cysteamine or 2-mercaptopropylamine during a long period of time showed lesser efficacy. WR 2721 which did not penetrate the brain exhibited only a feeble radioprotection. The imperviousness to straight active aminothiols may be compensated by the diffusion of their precursors across the blood brain barrier and by their speed of hydrolysis, yielding active aminothiols during a short period of time between their administration and the irradiation.

Mice's rectum radioprotection: comparative efficacy of a series of aminothiols and aminothiol precursors.

In mice, in a test of rectal gamma irradiation, cysteamine and cysteine are poor radioprotectors relative to thiazolanes or WR 2721. Among the tested prodrugs, 2-isopropyl 1,3-thiazolane was nearly as efficient as WR 2721 as soon as 15 minutes after its administration. The guarantee of radioprotection is the effective presence of the active aminothiols in the intracellular room during the irradiation. In this study, enterocytes of the rectal mucous membrane were not sufficiently permeable to exogenous cysteine or cysteamine. The cell imperviousness to these straight active aminothiols was compensated by the diffusion of their precursors across the membrane.

Percutaneous absorption of 5-iodo-2' deoxycytidine in the hairless rat and in man.

A study of percutaneous absorption of the anti-herpetic agent 5-iodo-2' deoxycytidine (IDC) was performed in vitro on the rat and on man and in vivo on the rat, using samples of normal skin and skin stripped of its stratum corneum. With normal skin, absorption was 1.84 cm.h1 10(-4) for the rat and 0.33 cm.h1 10(-4) for human skin; when the stratum corneum was absent, absorption was approximately 15 times higher. The results are discussed in terms of efficacy and toxicity of the drug.

Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.

Molecular biotransformation of 2-phenylthiazolidine (1) and its m-bromo derivative (2) in the mouse is followed by autoradiographic studies and assessed by analysis of urinary metabolites. Cysteamine (4) is one of the metabolites of compounds 1 and 2. Radioprotective activity and efficacy over a period of time of 1, 2, and 4 correlate closely with distribution and metabolism.